Identification of an Immune Tolerance Reaction in Response to Pretreatment With Frozen Pancreatic Tissue in Islet Cell Transplantation in Rats

OBJECTIVES: Whereas transplantation of insulin-secreting pancreatic islets may provide long-term control of glucose metabolism in patients with diabetes mellitus, transplant rejection remains a problem. In this study, we tried pretreatment with frozen pancreatic tissue in a rat model of islet cell transplantation to determine whether induction of immune tolerance is feasible. METHODS: Isolated islet cells from Wistar rats were transplanted into the spleen of recipient rats that were sensitized and rats that were not sensitized with frozen pancreatic tissue. Spleens were analyzed histologically and then examined immunohistochemically for expression of insulin, a pancreas-specific gene. With the use of cDNA primers for proinsulin, RT-PCR was performed to detect islet cells in the spleen. RESULTS: Although islet cells were present in spleens at posttransplantation day (PTD) 1, islet cell clusters in recipients without pretreatment were markedly destroyed on PTD 14 on histologic examination. In contrast, islet cell clusters in recipients sensitized with frozen pancreatic tissue appeared similar to those at PTD 1 even at PTD 14. Proinsulin gene expression was found to be specific to pancreatic tissue. In recipients sensitized with frozen pancreatic tissue, proinsulin gene expression was identified in recipient spleens, even at PTD 14, whereas it was undetected in the absence of pretreatment. In recipients transplanted with islet cells and treated simultaneously with frozen pancreatic tissue, proinsulin gene expression was completely eliminated. The immunohistologic study also showed the presence of insulin-producing islet cells in the spleens of rats sensitized with frozen pancreatic tissue. CONCLUSIONS: Inhibition of the immune reaction in transplant rejection may be mediated by pretreatment with frozen donor tissue.